The overarching goals of this R01 proposal are to leverage extensive existing clinical imaging data from a well- characterized cohort of older adults to improve scientific understanding of potential mechanisms by which anticholinergic medications (Aim 1) and glucose metabolism (Aim 2) lead to dementia and Alzheimer?s disease risk, and to provide a valuable resource that characterizes longitudinal changes in brain structure over time for this cohort of older adults (Aim 3). The proposal builds on the resources of the Adult Changes in Thought (ACT) study. ACT is situated within Kaiser Permanente Washington, known until February 2017 as Group Health, which has extensive clinical data resources including laboratory data stretching back to 1988 and pharmacy data stretching back to 1977. These data have enabled study investigators to develop longitudinal exposure models to identify risk factors for Alzheimer?s disease and dementia, including strong anticholinergic drugs (Aim 1) and glucose levels (Aim 2). Little is known about imaging correlates of these exposures. Some 2300+ clinical MRI scans have been performed on 1432 ACT participants but they currently are stored in records departments at dozens of hospitals and are not available for research. The investigators propose to reclaim the scan data for research and to obtain follow-up scans on living participants with a single existing scan. This economical approach will enable the investigators to obtain longitudinal (at least 2 year and in most cases much longer interval) imaging data on over 600 well-characterized study participants. The investigators propose to have trained neuroradiologists apply NIH Neuroimaging Common Data Elements (CDEs) to extract data from these scans, and will use image thresholding software to robustly measure volumes of large structures such as ventricles and total brain. The investigators will use these data in Bayesian modeling approaches to test hypotheses regarding the effects of anticholinergic medications on changes in ventricular enlargement and brain atrophy (Aim 1) and regarding the effects of high glucose levels on white matter hyperintensities (Aim 2). The investigators propose to store de-identified raw scan data, imaging CDEs, and data gleaned from brain volume analyses at the Laboratory of Neuro Imaging (LONI) to ensure promulgation to the broader research community (Aim 3).